The use of dietary supplements has become an increasingly common approach to obtaining and maintaining good-health. One of these dietary supplements, Coenzyme Q, is a vitamin-like substance which is used to treat congestive heart failure and other cardiac problems. Coenzyme Q is the best known of a group of lipophilic quinones which have the capacity to transfer reducing equivalents or electrons within a lipid phase of cellular membranes. Other quinones of this general lipophilic type found in cells are of diverse species. A few include, for example, rhodoquinone, menaquinone, plastoquinone, chlorobiumquinone, thermoplasmaquinone and phylloquinone. See, Collins, 1985, Methods in Micobiol. 18: 329-36′0. It is postulated that the diene dione chemical structure of these compounds provides a platform for the transfer of one or two electrons and associated protons within the lipid bilayers of cells or to and from hydrophobic redox centers in proteins.
Reduced benzoquinones in general are effective reductants for oxygen or lipid radicals. Early studies showed that reduced coenzyme Q is an effective antioxidant. See, Mellors and Tappel, 1996, J. Biol. Chem., 241: 4353-4356. Reduced coenzyme Q now appears to function as part of a complex chain of antioxidant activity. The most important role of coenzyme Q can be in reduction of radicals of α-tocopherol and ascorbate formed when these antioxidants are oxidized by oxygen or carboxyl radicals. There are no enzymes for direct reduction of tocopheryl radical or external ascorbate radical, but there are enzymes in all membranes which can reduce coenzyme Q and the reduced coenzyme Q can reduce the tocopheryl or ascorbate radicals to restore tocopherol or ascorbate. Without the support of enzymes to reduce coenzyme Q, the reduced coenzyme Q would not be a very effective antioxidant because the semiquinone formed by interaction with lipid or oxygen radicals is readily autooxidized with formation of a superoxide radical.
The enzymes involved in coenzyme Q reduction are the primary dehydrogenases for succinate. NADH or other substrates in mitochondria, the NADH cytochorome b5 reductase in endo and plasma membranes and DT diaphorase or NADPH dehydrogenase enzymes primarily located in the cytosol. Villalbe, et al., Proc. Natl. Acad. Sci. 92:4887-4891 (1995); Beyer, et al., Molec. Aspects Med., 18(S): 15-23 (1997); and Kishi, et al., Molec. Aspects Med., 18(S): 71-77 (1997).
Coenzyme Q in endo membranes or plasma membranes is extensively in the reduced form, most of the coenzyme Q in total rat and human tissue is in the reduced form and most of the coenzyme Q in serum is in the reduced state. See, Takahashi, et al., Lipids, 28: 803-809, (1993); Äberg, et al., Arch. Biochem. Biophys., 295: 230-234 (1992); and Yamamoto and Yamashita, Molec. Aspects Med., 18 (S) (1997).
Studies performed to date have not focused on the differential uptake and bioavailability of one form of coenzyme Q versus another form of coenzyme Q. Nor has the art recognized the desirability of using ubiquinol as an active pharmacological agent to enhance the bioavailability of coenzyme Q from oral and other formulations.